AFP is expressed during foetal development and is the main component of foetal serum. During development the protein is produced at very high levels by the yolk sac and liver and is later repressed. AFP expression is frequently reactivated in hepatocellular carcinoma (Butterfield et al. J Immunol., 2001, Apr. 15; 166(8):5300-8) and high levels of the protein are used as a diagnostic marker for the disease.
Hepatocellular carcinoma has one of the lowest reported 5 year survival rate of all malignancies in the US, global annual incidence is 1.2 million and is likely to increase due to the pandemic of Hepatitis B and C. Treatment typically involves surgery, however this is only beneficial if carried out in the early stages of the disease. New treatments are therefore desirable.
There are four known epitopes derived from AFP: AFP158, AFP137, AFP325 and AFP542 (Butterfield et al. J Immunol., 2001, Apr. 15; 166(8):5300-8 and Butterfield et al. Cancer Res. 1999, 59: 3134-3142). The HLA-A2 restricted AFP158 peptide FMNKFIYEI (SEQ ID No: 1) provides a suitable target for novel immunotherapeutic interventions; this peptide is naturally processed and has been eluted from HepG2 (HLA-A2 positive) liver carcinoma lines and detected by mass spectrometry (Butterfield et al. J Immunol., 2001, Apr. 15; 166(8):5300-8). T cell clones have been raised against AFP158 (and AFP137) (Pichard et al. J Immunother. 2008 April; 31(3):246-53). However, T cell receptors which recognize this peptide have not been reported.
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